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An approach to neurological disorders in a kidney transplant recipient
Priti Meena, Vinant Bhargava, Devinder Rana, Anil Bhalla, Ashwani Gupta
Sir Ganga Ram Hospital, Rajendra Nagar, New Dehli, India
Correspondence:
Priti Meena
Sir Ganga Ram Hospital
Rajendra Nagar
New Dehli, India
110092
Kidney360 Publish Ahead of Print, published on June 16, 2020 as doi:10.34067/KID.0002052020
Copyright 2020 by American Society of Nephrology.
Abstract
Kidney transplantation is the preferred modality of choice for treatment in patients with end-
stage kidney disease. However, there are associated complications that arise from
immunosuppressive medications, infections, and associated co-morbidities. Neurological
disorders frequently develop in kidney transplant patients, in turn, increasing the associated
morbidity and mortality. This review discusses the common neurological disorders following
kidney transplantation, including infections, cognitive decline, drug-related, malignancy,
seizure, and other neurological complications.
Introduction
Kidney transplantation is the desired modality of treatment in patients of end-stage kidney
disease (ESRD). It offers better survival and quality of life as compared to hemodialysis and
peritoneal dialysis. Despite these advantages, transplant recipients are susceptible to
complications that impede the quality of life and add to the financial burden. Neurological
diseases frequently develop in kidney transplant recipients and increase morbidity.
Neurological diseases after kidney transplantation are frequently underdiagnosed and have
been reported in up to 30% to 60% of patients. (1) Noteworthy, in a systematic review and
meta-analysis by Mohammadi et al. , the total prevalence of neurological disorders in 4674
patients following kidney transplantation was 7.9% (2)
This review attempts to classify the neurologic complications in kidney transplant recipients
(KTR) under the following categories: (a) pre-existing neurological conditions (b) early
neurological complications (c) subacute and d) late neurological complications and highlights
various neurological complications related to infections, medications, malignancies and other
comorbid conditions.
Pre-existing neurological disease
Neurological disease in renal failure may not be unveiled until transplantation. Associated co-
morbidities like vascular calcification, malnutrition, chronic inflammation, cerebrovascular
accidents, diabetes mellitus, hypertension, and other underlying diseases such as systemic
lupus erythematosus predispose these patients to neurological syndromes. Ischemic stroke is
responsible for both acute neurological deficits or subclinical, gradually worsening cognitive
impairments. Diabetes mellitus affects peripheral nerves resulting in painful sensory
neuropathy. Systemic lupus erythematosus has a wide spectrum of neurological manifestations,
for example, headache, seizures, chorea, with cognitive dysfunction, myelopathy, meningitis,
and mononeuropathy. (3) Patients with infections like HIV can experience dementia,
neuropathies, and vacuolar myelopathy. (4) Longstanding uremia causes axonal, symmetrical,
sensorimotor, length-dependent, polyneuropathy that does not entirely resolve even after the
improvement of renal function. Autonomic dysfunction is another complication of uremia,
which causes orthostatic hypotension, impotence, heart rate variability, exercise intolerance,
and gastrointestinal intolerance. (5) Factors like age, diabetes mellitus, inflammation, stroke,
oxidative stress, and decreased cerebral perfusion, leading to cerebral ischemia during
hemodialysis, make ESRD patients more vulnerable to cognitive impairment and dementia as
compared to the general population. (6)
Neurological illnesses may manifest at any time post-transplantation. Immediate neurological
complications occurring post-renal transplantation surgery are associated with several
diagnostic possibilities. They can affect both the central nervous system (CNS) and the
peripheral nervous system (PNS).
CNS Dysfunction: Following transplant surgery, KTR may exhibit mild symptoms like
behavioral changes and confusion due to perioperative sedation, but they may be as severe as
encephalopathy or coma resulting from hypoxic-ischemic insult. The patients requiring
intensive care unit (ICU) may develop psychosis within 2–5 days after surgery. Neuroimaging
with computed tomography (C.T.) scan or magnetic resonance imaging (MRI ) scan aid in
diagnosis. (7) Psychosis usually resolves with environmental reorientation; rarely neuroleptics
are required.
Electrolyte Imbalance: Abnormalities in electrolytes and acid-base is a regular finding after
renal transplantation. The most frequent post-transplant metabolic disturbances are
dysnatremia, hyperkalemia, hypomagnesemia, hypophosphatemia, and metabolic acidosis.
Serum sodium of less than 120 mEq/L may lead to confusion, disorientation, or generalized
tonic-clonic seizures. Severe hypomagnesemia may also manifest as confusion, muscle
weakness, tremor, tetany, and seizures. (8) The correction of existing electrolyte imbalance
improves attributable neurological symptoms. Sodium correction should be done meticulously
as a rapid correction (> 10 mEq/L over 24 hours) may lead to central pontine myelinolysis.
Hypertensive encephalopathy: Hypertensive encephalopathy in the immediate post-
transplant period is caused by uncontrolled high blood pressure. It may result from drugs
(steroids/ calcineurin inhibitor), allograft rejection, renal artery stenosis, or volume overload.
(9) Hypertensive encephalopathy is often associated with posterior reversible encephalopathy
syndrome (PRES). It has characteristic findings on MRI, which includes vasogenic edema in
bilateral deep cortical and subcortical regions of the parietal and occipital lobes. Other risk
factors contributing to PRES are young age, high doses of corticosteroids, calcineurin
inhibitors (CNI), and longstanding uremia before transplant. PRES usually presents with
convulsion, headache, visual defects, and altered mental state. Management involves the
removal of offending drugs and anti-hypertensive medication for blood pressure control. (10)
Peripheral nervous system dysfunction: During renal transplantation, the incidence of
peripheral nerve injuries is seen in up to 5% of patients. (11) The femoral nerve, lateral femoral
cutaneous nerve, and the lumbosacral plexus are the commonly affected sites. (12) Damage to
the nerve can occur either by compression by a local hematoma formation or stretching of the
nerve from prolonged retraction. Rarely, acute femoral neuropathy may develop in 0.1–3% of
patients. (13) It may not be noticed until the patient attempts to ambulate and is typically
apparent within 24–48 hours post-surgery. Ischemia, due to the “steal phenomenon” during
anastomosis of the renal graft artery to the internal iliac artery, is another mechanism of nerve
damage as the proximal end-to-end anastomosis diverts blood away from the vasa nervosum.
(14) On examination, unilateral weakness on knee extension, absent patellar reflex, and
decreased sensation on the anterior medial aspect of the thigh may be found. The patient may
also complain of numbness over the lateral aspect of the thigh due to injury of the lateral
femoral cutaneous nerve, which is present in 2.4% of patients in one
series. (15) Lumbosacral plexopathy can also occur in cases where the internal iliac artery is
used for graft revascularization. The patient complains of pain in the buttock, and examination
reveals weakness of ankle dorsiflexion or proximal leg weakness. Neuropathies are usually
self-limiting and resolve entirely, which can take several months; however, there may be
incomplete recovery. (12-13,16)
Seizure
The reported incidence of seizure in KTRs is approximately 17.6 %. (17) Seizure in a KTR
may be related to numerous etiologies such as electrolyte disorders, withdrawal of antiepileptic
drugs, CNI toxicity including PRES, liver dysfunction, cerebrovascular accidents, infections,
and brain tumors. Convulsions are commonly reported during the immediate 24 hours post-
transplant surgery; they are usually due to changes in plasma osmotic pressure and serum
sodium. (18) For identification of etiology imaging with C.T. or MRI head are helpful. The
electroencephalogram plays an essential role in excluding non-epileptic seizures (such as
myoclonus) and determines the type of seizure. To rule out an infectious cause, CSF analysis
should be performed. An approach to a seizure in a KTR is illustrated in figure 1. The mainstay
for seizure management in a KTR is to identify and treat the underlying etiology in addition to
initiating antiepileptic drug (AED). The selection of an AED for a KTR is complicated by
factors like drug interactions, tolerability, metabolism, and excretion. Drugs like barbiturates,
phenytoin, and carbamazepine have significant drug interactions with immunosuppressive
medications, as they induce hepatic cytochrome P450 enzymes leading to increase in the
metabolism of CNIs and steroids (19) Newer AEDs like levetiracetam, lacosamide, gabapentin,
and pregabalin have favorable side effect profiles and minimal drug interactions. A brief
summary of the pharmacokinetics of important AEDs is shown in table 1.
Subacute neurological complications
Infections
About 5-10 percent of KTRs suffer from CNS related infections at any time post-
transplantation, resulting in a mortality rate of 44-77%. (20) Infections account for more than
thirty percent of patients manifesting with signs and symptoms of the neurological illness (21).
The probability of infection from a pathogen varies with the duration post-transplantation.
Infections in the early post-transplantation period (< 1 month) are usually
nosocomial (acquired pathogens) or donor-derived. Subsequently, after five months, infections
due to opportunistic organisms develop. (22) The risk of developing an infection depends on
two crucial factors: 1) epidemiologic exposure (from the community or hospital) with the
organism; 2) net immunosuppressive state of the patient. Decreased T-cell immunity owing
to immunosuppressive medications is primarily responsible for infectious complications.
Treatment of graft rejection, diabetes mellitus, malnutrition, and poor graft functions are other
important contributing factors. (23) Clinical presentation of these patients varies from fever,
meningismus, headache to the altered sensorium, and seizure. In KTR, the diagnosis of CNS
infection may be challenging as they may present with minimal signs and symptoms
attributable to immunosuppressive therapy. CNS infections can be categorized as meningitis,
encephalitis, and focal brain abscess. Table 2 summarizes common CNS infections experienced
in KTR, with methods of diagnosis and treatment strategies. (22-24)
Progressive Multifocal Leukoencephalopathy (PML)
PML is a fatal and cataclysmic condition of CNS caused by the John Cunningham virus, a
human polyoma family virus. The incidence of PML after kidney transplantation is 0.027%,
with a median time of seventeen-month following transplant. (25) Visual deficits, mental
deficits (cognitive changes, emotional liability, and memory loss), motor weakness, and seizure
are the usual complaints in patients with PML. Still, it can be relentlessly progressive and
devastating, causing mortality within months to a year. Its spread to the brain results in cerebral
white matter demyelination and oligodendrocytes lysis. MRIs show multifocal, asymmetric
lesions in cortical and subcortical areas with a minute or no mass effect or enhancement
typically involving parieto-occipital regions. (26) Brain biopsy is the gold standard method for
diagnosis, but diagnosis can also be made by CSF analysis for J.C. virus DNA by PCR
technique. (27) Patients with PML have a fatal outcome, and currently, there is no effective
treatment strategy. However, cytarabine and interferons have been tried in PML with no clear
success. (28-29)
Drug toxicity
Calcineurin Inhibitors: Tacrolimus (Tac) and Cyclosporine (CsA) form the backbone of
immunosuppression in a KTR. They inhibit calcineurin activation and block interleukin-2
production. The overall estimated frequency of neurological adverse effects may vary from
10%-28%. (30) Various published studies have shown that tacrolimus is more frequently and
severely associated with neurotoxicity as compared to cyclosporine. (31) The timing of CNS
side effects is usually within the first month after initiation, and they are more frequent at higher
doses; however, they can occur even at therapeutic levels (32). The severity of symptoms
ranges from mild such as tremor, ataxia, agitation, confusion, and nightmares to severe as
encephalopathy, convulsion, and coma. Visual hallucinations and cortical blindness may also
seldom occur in a KTR on CNI. (33) (Table 3) CsA and Tac may have deleterious effects on
the peripheral nervous system. Both the nerve and the muscle can get affected. Cases of axonal,
demyelinating, and multifocal demyelinating neuropathy have been reported to be more severe
with tacrolimus. (34)
Mechanisms of neurotoxicity:
• Calcineurin is also expressed in several areas of the brain: cerebral cortex, striatum,
substantia nigra, cerebellum, and hippocampus. Both CsA and Tac are highly lipophilic
and bound to low-density lipoprotein, so they can cross the blood-brain barrier and
damage the white matter. (35)
• CNIs cause an increase in endothelin expression and decrease nitric oxide production.
By disrupting endothelin integrity, CsA and Tac gain access to astrocytes and cerebral
vascular smooth muscle, invoking vasoconstriction and vasospasm. (36)
• Disruption of the blood-brain barrier and cytotoxic effect on the vascular endothelium
results in leakage of fluid into the interstitium, resulting in vasogenic edema.
• CsA and Tac may also cause neurotoxicity by alteration in mitochondrial function and
ensuing apoptotic or necrotic cell death from activation of anaerobic glycolysis,
proteases, phospholipases, and generation of free radicals. (37)
Predisposing factors for the development of CNI induced neurotoxicities are advanced liver
failure, low cholesterol levels, elevated CsA or tac blood levels, hypomagnesemia, and steroids.
(33) The use of delayed-release formulations, minimum therapeutic doses, strict monitoring of
blood levels, and vigilance to pharmacological interactions may reduce drug-induced
neurotoxicity. Some times change CNI to mTOR inhibitors, or belatacept may be required in
case of severe and no improvement in symptoms.
• Posterior Reversible Encephalopathy Syndrome
The overall estimated incidence of PRES in solid organ transplantation recipients is 0.5%–5%
and is more common with the use of tacrolimus. (38) MRI brain findings in PRES have been
already mentioned above. The characteristic subcortical edema is the result of endothelial cell
damage promoted by loss of autoregulation in the posterior circulation. The following criteria
may help establish the diagnosis of calcineurin inhibitors associated PRES: (1) clinical features
(headache, changes in mental status, seizures and visual disturbances) after excluding other
possible causes such as infection, metabolic disorders, and structural CNS lesions and (2)
characteristic findings C.T. or MRI brain of subcortical white matter lesions. (39) This
syndrome is potentially reversible and should be diagnosed as early as possible. It usually
responds to cessation or lowering the dose of the drug, additionally controlling hypertension
and convulsions.
• Calcineurin-Induced Pain Syndrome
Calcineurin-induced pain syndrome is characterized by incapacitating bilateral leg pain sparing
the hip areas. The reported incidence in transplant patients is 2% to 14% and usually presents
within the first year post-transplantation. (40) The most common affected areas are knee and
feet. Symptoms may worsen with physical activity, stress and may improve with resting.
Imaging studies show bone marrow edema in affected areas. The exact mechanism is yet to be
elucidated, but it is postulated that calcineurin inhibitors affect sensory neural function by
regulating two-pore potassium channels, leading to an alteration in neuronal resting membrane
potential. The syndrome usually is self-resolving, but according to some anecdotal reports,
calcium channel blockers are beneficial. (41)
Corticosteroids can cause neuropsychiatric symptoms, such as insomnia, impaired
concentration, mood changes, irritability, mania, psychosis, and depression. Symptoms usually
begin within days to weeks after treatment initiation. With long term use, the peripheral
nervous system can also be involved, and proximal myopathy can occur, which may not
completely resolve after cessation of the drug. (42)
Mycophenolate mofetil (MMF) is rarely associated with neurotoxicity. Headache is one of
the few side effects associated with the use of MMF. (43)
Mammalian Target of Rapamycin Inhibitors (mTOR inhibitors) - Neurotoxicity is
infrequent with sirolimus and everolimus. Few cases of reflex sympathetic dystrophy and
PRES have been reported with sirolimus and everolimus, respectively. (44,45)
Bortezomib can cause painful sensory neuropathy. (46)
Neurologic side effects of immunosuppressants used in kidney transplantation (Table 4)
Chronic neurological complications
Cerebrovascular Disease
Cerebrovascular accidents (CVA), including ischaemic, hemorrhagic stroke, and transient
ischemic attacks, are the most common chronic neurological complication in a KTR. U.S.
Renal Data System data showed that the incidence of CVA in a KTR is 5% during the first year
post-transplant and 9.4% in the second year. (47) A study done on 1600 KTRs revealed that
60.3% of patients died with a functioning graft, and stroke was the second-highest cause of
mortality after infections. (48) Cerebral hemorrhages can be catastrophic and fatal. Various
factors like long-term use of steroids, hypertension, diabetes mellitus, smoking, old age, poor
graft function, obesity, dyslipidemia, and peripheral arterial disease contribute to accelerated
atherosclerosis and increased risk of stroke in a KTR. Patients with polycystic kidney disease
are at a higher risk of developing a hemorrhagic stroke. (49) In a KTR with ischemic stroke,
other possibilities like fungal infections (aspergillosis and mucormycosis) should also be
excluded as the hyphae can invade cerebral arteries with distal embolization. Correction of
reversible risk factors like treatment of hypertension and dyslipidemia, cessation of smoking
and alcohol, controlling diabetes is crucial in improving outcomes. The use of anticoagulation
to prevent cardioembolism in patients with atrial fibrillation should be considered as per risk
to benefit assessment. (50)
Cognition
Improvement in cognitive function following kidney transplantation is variable, as some
studies suggested improvement only to some extent, and others have indicated exacerbation of
cognitive decline. (51) Impairment in multiple domains like verbal learning, memory, and
executive functioning was found to be higher in KTR as compared to the general population.
(52) Cognitive impairment adversely impacts daily living. Defective memory and executive
function may lead to a breach in adherence to immunosuppressive medications. It also
diminishes the quality of life and employment rates while escalating hospital admissions,
financial burden, morbidity, and mortality. Metabolic and vascular changes due to prolonged
exposure to comorbid medical conditions, developed during the dialysis period, neurotoxicity
from medications such as CNI or steroids, diabetes, higher baseline frailty, malnutrition, are
some important factors responsible for cognitive impairment in a KTR. (53) Improved graft
function results in amelioration of processing speed, convergent thinking, executive, and
attention functioning. (54) Treatment of cognitive impairment involves comprehensive care
and is usually supportive. It includes management of chronic comorbid conditions, treatment
of other associated factors such as depression, optimal effective immunosuppression strategies.
Polypharmacy and the use of psychotropic drugs should be deterred.
CNS Malignancy
Various CNS malignancies, including post-transplant lymphoproliferative disorders (PTLD),
oligodendrogliomas, astrocytomas, lymphomas, and glioblastomas, have been reported in
previously published literature in post-transplantation settings. (55) Of all PTLD cases, CNS
is involved in approximately 7–15% of cases. (56) In a study by Snanoudj R et al. done in 25
KTRs, the median duration of diagnosis post-transplant was eighteen months. (57) In contrast
to this, an analysis of 34 patients of primary CNS lymphoma by Cavaliere et al. reported a
median time of 4.4 years post-transplantation. The most common presenting symptom was a
focal neurological deficit. (58) Other symptoms are headache, seizures associated with raised
intracranial pressure. Less frequently, visual defects and spinal cord lesions may be present.
Two critical factors determining the risk of development of primary CNS lymphoma are (1)
immunosuppression load of the patient; and (2) Epstein–Barr virus seropositivity. According
to some studies, female sex, high lactate dehydrogenase level, poor performance status, and
resistance to initial therapy are predictors of inferior survival. Treatment strategies typically
involve reduction or cessation of immunosuppression
medications and the use of rituximab. Systemic and intrathecal chemotherapy, radiation, and
surgery may be used adjunctively according to the stage of malignancy. (59)
Conclusion
Neurological manifestations in a post-kidney transplant recipient is a common and frequent
cause of mortality and morbidity. It is rewarding to identify the cause and guide the treatment
accordingly. Multiple etiologies need to be considered, and infection is the commonest cause
in post-transplant settings. A good physical examination and history help to identify most of
these.
Author Contributions
P Meena: Writing - original draft
V Bhargava: Resources; Software; Writing - review and editing
D Rana: Resources; Supervision
A Bhalla: Conceptualization; Formal analysis
A Gupta: Supervision; Validation
Disclosure
All authors have nothing to disclose.
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Legends
Table 1. Summary Of The Pharmacokinetics Of Antiepileptic Drugs.
Table 2. Common Cns Infections Post Renal Transplantation.
Table 3: Neurological Side Effects Of Calcineurin Inhibitors.
Table 4. Neurologic Side Effects Of Immunosuppressants Used In Kidney Transplantation.
Figure 1: An Approach To Seizure In A Renal Allograft Recipient.
Table 1. Summary of the pharmacokinetics of antiepileptic drugs.
Drugs Metabolism Route of Elimination
Renal toxicity
Inducers of cytochrome P450 (CYP) enzymes
Phenobarbital Inducer of CYP3A Hepatic/renal Interstitial nephritis; anemia; hypovitaminosis D
Phenytoin Inducer of CYP3A, metabolized by CYP2C9
Renal -<5% Acute interstitial nephritis; decrease ADH release
Carbamazepine Inducer of CYP3A Hepatic Acute interstitial nephritis; hyponatremia (SIADH)
Lamotrigine Induces CYP34A Hepatic Acute interstitial nephritis
Topiramate weak inducer of CYP3A4 Renal Renal tubular acidosis; nephrolithiasis
Inhibitors of cytochrome P450 (CYP) Enzymes
Valproate Hepatic(CYP450) metabolism,inhibit CYP2C9
Hepatic Tubulointerstitial nephritis; Fanconi syndrome.
Felbamate Inhibit CYP450
Renal Rare incidence of renal stone
No drug interactions
Gabapentin None Renal -
Levetiracetam None Renal Hypokalemia; hypomagnesemia
Table 2. Common CNS Infections Post Renal Transplantation
Disease Organism Diagnosis Treatment
Meningitis
Headache,
fever, altered
mental
sensorium,
cranial nerve
palsy, neck
rigidity
Bacterial Listeria
monocytogenes,
Haemophilus
influenza,
Neisseria
meningitides, and
Streptococcus
pneumonia.
· Cerebrospinal fluid (CSF)
-pleocytosis, increased
protein, and reduced
glucose
· Gram stain positive
· Rapid antigen latex
agglutination test
· PCR for Neisseria
meningitides and
Streptococcus
pneumoniae
Antibiotics based
on culture and
sensitivity
Mycobacterium
tuberculosis
· CSF- Acid-fast bacilli +
· Raised adenosine
deaminase
· Raises total
leucocyte with
lymphocyte
predominance, low
glucose, increased protein
Antitubercular
therapy
Fungal CSF- lymphocytic or monocytic pleocytosis, elevated protein, and low
glucose
Cryptococcus
neoformans
· CSF cryptococcal antigen,
India ink I.V Amphotericin
B and fluconazole
Aspergillus spp. · Galactomannan assay
· (1,3)-beta-D-glucan assay
· DNA PCR assay in serum
or BAL samples
Voriconazole
Amphotericin B
· Branching, septated
hyphae
Candida spp · Pseudohyphae and
budding yeast Fluconazole
Echinocandin or
Amphotericin B
Encephalitis:
Headache ,
seizures, focal
neurological
deficit, altered
mental status,
cranial nerve
palsy
Cytomegalovirus · CSF PCR positive
· MRI-Enhancing
ventriculoencephalitis
Ganciclovir
Varicella-zoster
virus
· MRI- Mixed lesion
(ischemic or hemorrhagic
infarcts)
· Demyelinatinag lesions at
grey-white matter junction
· CSF PCR positive
Acyclovir
Ganciclovir
Human herpes
virus-6
· CSF PCR positive
· Focal or diffuse
encephalitis
Ganciclovir or
foscarnet
Focal Brain
Infections:
Parasite Toxoplasma Gondi · MRI- Multiple ring-
enhancing lesions,
predilection to basal
ganglia, thalami, and
corticomedullary junction
Pyrimethamine
and folinic acid
Headaches,
seizures, and
focal
neurological
deficits
Bacterial Nocardia
asteroides
· Gram-positive, weakly
acid-fast, branching rod-
shaped bacteria
· MRI- Single or multiple
lesions with contrast
enhancement and little
mass effect
Trimethoprim/
sulfomethoxazole
and neurosurgical
intervention
Fungal Mucormycosis,
Aspergillosis,
Candida
Cryptococcosis,
Begin with paranasal sinuses,
producing periorbital edema
and may invade the
intracavernous carotid artery,
Cerebral artery emboli,
mycotic aneurysm and stroke
Antifungals
Table 3: Neurological Side Effects Of Calcineurin Inhibitors
Neurological Side Effects Of Calcineurin Inhibitors
Severity Central toxicity Peripheral toxicity
Minor Insomnia, visual disturbances, headache,
and mood changes
Paresthesias, peripheral neuropathy, and
myopathy.
Major PRES, akinetic mutism, toxic
encephalopathy, and convulsions
Axonal and demyelinating neuropathy,
Guillain–Barré syndrome.
Table 4. Neurologic Side Effects Of Immunosuppressants used in Kidney Transplantation
Drugs Side effects
Calcineurin inhibitors
Mild: Tremor, headache, insomnia, vivid dream imagery, photophobia
Moderate: visual and cortical disturbances
Severe: Encephalopathy, convulsion, coma, and flaccid quadriparesis
Steroids Insomnia, anxiety, psychosis, myopathy, mania, depression
Bortezomib Distal peripheral neuropathy
Mammalian target of rapamycin inhibitor
Sympathetic dystrophy, rarely PRES and possible potentiation of calcineurin-inhibitor toxicity
Belatacept Central neurological system
Post-transplant lymphoproliferative disorder
Alemtuzumab Sensorimotor polyneuropathy and myelitis
Rituximab Progressive multifocal leukoencephalopathy
Figure 1: An Approach To Seizure In A Renal Allograft Recipient.